Paediatric norms for photopic electroretinogram testing based on a large cohort of Chinese preschool children.

OBJECTIVE: Full-field electroretinogram (ffERG) is an objective test to determine the electroretinal activities in response to light stimulation for investigating retinal physiology and diagnosing retinal diseases. This study aimed to establish a reference data set of photopic electroretinogram (ERG) of Chinese preschool children in Hong Kong to facilitate clinical and research studies. METHODS AND ANALYSIS: Preschool children aged 3-7 years with normal vision were recruited from local kindergartens. Eye examinations, including cycloplegic spherical equivalent refraction (SER), axial length (AL) and keratometry (K) measurements, were performed. ffERGs of the International Society for Clinical Electrophysiology of Vision (ISCEV) standard photopic flash and 30-Hz flicker protocols were measured using RETeval with Sensor Strip skin electrodes. ERG waveform characteristics were extracted, and relationships between ERG, age, SER, AL and K were evaluated. RESULTS: A total of 479 children completed the measurements (mean age: 5.0±0.9 years, 45.5% female). Mean, 95% CIs, 5th-95th percentile range of the ERG parameters were reported. Age was positively associated with amplitudes of b-wave and 30-Hz flicker (p<0.01), but negatively associated with implicit times of b-wave and 30-Hz flicker (p<0.01). AL was significantly associated with all amplitudes of a-wave, b-wave and 30-Hz flicker (p≤0.01) and implicit time of both a-wave and 30-Hz flicker (p<0.05). K was positively associated only with 30-Hz flicker amplitude (p=0.01), and no association between all responses and SER. CONCLUSION: Reference data set of photopic ERG of Chinese preschool children was established. Cross-sectional investigations revealed associations between ERG, age, SER and AL, which were speculated to further implicate the role of retina in refractive error development.

Long-Term Effects on Retinal Structure and Function in a Mouse Endothelin-1 Model of Retinal Ganglion Cell Degeneration.

Purpose: To study the long-term effects of endothelin-1 (ET-1)-induced retinal pathologies in mouse, using clinically relevant tools. Methods: Adult C57BL/6 mice (7-9 weeks old) were intravitreally injected with PBS (n = 10) or 0.25 (n = 8), 0.5 (n = 8), or 1 nmol ET-1 (n = 9) and examined using electroretinogram, optical coherence tomography (OCT), and Doppler OCT at baseline and postinjection days 10, 28, and 56. Retinal ganglion cell (RGC) survival in retinal whole mount was quantified at days 28 and 56. Results: ET-1 induced immediate retinal arterial constriction. The significantly reduced total blood flow and positive scotopic threshold response in the 0.5- and 1-nmol ET-1 groups at day 10 were recovered at day 28. A-wave magnitude was also significantly reduced at days 10 and 28. While a comparable and significant reduction in retinal nerve fiber layer thickness was detected in all ET-1 groups at day 56, the 1-nmol group was the earliest to develop such change at day 28. All ET-1 groups showed a transient inner retinal layer thinning at days 10 and 28 and a plateaued outer layer thickness at days 10 to 56. The 1-nmol group showed a significant RGC loss over all retinal locations examined at day 28 as compared with PBS control. As for the lower-dosage groups, significant RGC density loss at central and midperipheral retina was detected at day 56 when compared with day 28. Conclusions: ET-1 injection in mice resulted in a transient vascular constriction and reduction in retinal functions, as well as a gradual loss of retinal nerve fiber layer and RGC in a dose-dependent manner.

Functional and structural changes in the neuroretina are accompanied by mitochondrial dysfunction in a type 2 diabetic mouse model.

BACKGROUND: Diabetic retinopathy (DR), one of the leading causes of blindness and vision impairment, is suggested to exhibit functional and structural changes in retinal neurons as the earliest manifestation, which could be used to predict the progression of related angiopathy. While neural function and survival rely on proper mitochondrial function, and a growing body of literature has supported the role of mitochondrial dysfunction in the development of DR, how diabetes affects mitochondrial function in retinal tissue remains elusive. This study primarily aimed to investigate mitochondrial functional changes in a diabetic rodent model. We also characterized the early DR phenotype, in particular, neurodegeneration. METHODS: C57BLKsJ-db/db (db/db) mice (a type 2 diabetic mouse model) were used with their normoglycemic heterozygous littermates (db/+) serving as controls. Longitudinal changes in retinal function and morphology were assessed with electroretinography (ERG) and optical coherence tomography (OCT), respectively, at 9, 13, 17, and 25 weeks of age. At 25 weeks, the retinas were harvested for immunohistochemistry and ex vivo mitochondrial bioenergetics. RESULTS: Decreased ERG responses were observed in db/db mice as early as 13 weeks of age. OCT revealed that db/db mice had significantly thinner retinas than the controls. Immunohistochemistry showed that the retinas of the db/db mice at 25 weeks were thinner at the outer and inner nuclear layers, with lower photoreceptor and cone cell densities compared with the db/+ mice. The number of rod-bipolar cell dendritic boutons and axon terminals was significantly reduced in db/db mice relative to the db/+ mice, suggesting that diabetes may lead to compromised synaptic connectivity. More importantly, the retinas of db/db mice had weaker mitochondrial functions than the controls. CONCLUSIONS: Our longitudinal data suggest that diabetes-induced functional deterioration and morphological changes were accompanied by reduced mitochondrial function in the retina of db/db mice. These findings suggest that mitochondrial dysfunction may be a contributing factor triggering the development of DR. While the underlying mechanistic cause remains elusive, the db/db mice could be a useful animal model for testing potential treatment regimens targeting neurodegeneration in DR.

Potential role of Lycium barbarum polysaccharides in glaucoma management: evidence from preclinical in vivo studies.

In recent years, the pharmacological benefits of herbal extracts have been revisited for their potential neuroprotective effects in glaucoma. The polysaccharides extracted from the fruits of Lycium barbarum L., or Lycium barbarum polysaccharides, exert their anti-aging effect through reducing oxidative stress, modulating the immune response, enhancing neuronal responses, and promoting cytoprotection. The therapeutic efficacy of Lycium barbarum polysaccharides in preserving retinal ganglion cells and their functions was demonstrated in a range of experimental models of optic neuropathies. These include the acute and chronic ocular hypertension models, the partial optic nerve transection model, and the ischemic-reperfusion injuries model. Based on these findings, Lycium barbarum polysaccharides appear to be a good candidate to be developed as a neuroprotective agent for treating multifactorial diseases. This review aims to present a comprehensive review on the latest preclinical evidence on the pre- and post-treatment benefits of Lycium barbarum polysaccharides in retinal ganglion cell neuroprotection. The possible mechanisms of Lycium barbarum polysaccharides mediating retinal ganglion cell neuroprotection will also be described. Moreover, the potential research gaps in the effective translation of Lycium barbarum polysaccharides treatment into clinical glaucoma management will be discussed.

Size of living space as a moderator for central and peripheral refractions in children.

Undesirable living environment may impose risk on myopia development. Furthermore, peripheral refractive error was suggested to contribute to juvenile eye growth modulation. This study aimed to investigate the interaction between peripheral refractive error and living environment in relation to central refractive status in Hong Kong schoolchildren. Central and peripheral refractive errors, axial length (AL), and corneal radius of curvature (CR) were measured in 573 schoolchildren (age 9.5 ± 0.9 years). The AL/CR ratio was used to represent the central refractive status, accounting for non-cycloplegic refraction. The relative peripheral refractive errors (RPRE) up to ± 20° eccentricities were converted into power vectors: spherical-equivalent error (SER) and J0 astigmatic components and fitted with quadratic equations. The second-order coefficients of SER (aSER) and J0 astigmatism (aJ0) and home size reported by parental questionnaires were analyzed to indicate their relationships with AL/CR. Our results showed that children with higher AL/CR lived in smaller homes (p = 0.01) and had a more hyperopic (p < 0.001) but less astigmatic RPRE (p = 0.01). We further analyzed the relationship between AL/CR with RPRE for children living in small (< 300 ft2), moderate (300-600 ft2), and large home sizes (> 600 ft2). Regardless of the home size, a higher AL/CR remained moderately correlated with a more hyperopic aSER (all p < 0.001). However, a higher AL/CR was associated with a more positive aJ0 only in children living in large homes, and the relationships were not significant for small and moderate home sizes. Linear regression models further indicated that home size was a significant moderator contributing to the relationship between AL/CR and aJ0. In conclusion, our results were consistent with previous studies, showing that children with axial myopia usually lived in smaller homes and had more hyperopic defocus and more positive J0 astigmatism. However, the relationship between peripheral astigmatism and axial refraction was modulated by the home size of Hong Kong schoolchildren. While peripheral astigmatism is hypothesized as a visual cue for axial refractive development in children, extrinsic environmental factors, such as home size, might interfere with the relationship and dominate refractive development.

Evaluating the performance of OCT in assessing static and potential dynamic properties of the retinal ganglion cells and nerve fiber bundles in the living mouse eye.

Glaucoma is a group of eye diseases characterized by the thinning of the retinal nerve fiber layer (RNFL), which is primarily caused by the progressive death of retinal ganglion cells (RGCs). Precise monitoring of these changes at a cellular resolution in living eyes is significant for glaucoma research. In this study, we aimed to assess the effectiveness of temporal speckle averaging optical coherence tomography (TSA-OCT) and dynamic OCT (dOCT) in examining the static and potential dynamic properties of RGCs and RNFL in living mouse eyes. We evaluated parameters such as RNFL thickness and possible dynamics, as well as compared the ganglion cell layer (GCL) soma density obtained from in vivo OCT, fluorescence scanning laser ophthalmoscopy (SLO), and ex vivo histology.

The effect of montages of transcranial alternating current stimulation on occipital responses-a sham-controlled pilot study.

Background: Transcranial alternative current stimulation (tACS) refers to a promising non-invasive technique to improve brain functions. However, owing to various stimulation parameters in the literature, optimization of the stimulation is warranted. In this study, the authors aimed to compare the effect of tACS electrode montages on occipital responses. Methods: In three montage sessions (i.e., Oz-Cz, Oz-cheek, and sham), 10 healthy young adults participated, receiving 20-min 2-mA alpha-tACS. Pattern-reversal visual evoked potentials (VEPs) were measured before tACS (T0), immediately after (T20), and 20 min (T40) after tACS. Normalized changes in time-domain features (i.e., N75, P100 amplitudes, and P100 latency) and frequency-domain features [i.e., power spectral density in alpha (PSDα) and beta (PSDß) bands] were evaluated. Results: In contrast to our hypothesis, the occipital response decreased immediately (T20) after receiving the 20-min tACS in all montages in terms of P100 amplitude (p = 0.01). This reduction returned to baseline level (T0) in Oz-cheek and sham conditions but sustained in the Oz-Cz condition (T40, p = 0.03) after 20 min of tACS. The effects on N75 amplitude and P100 latency were statistically insignificant. For spectral analysis, both PSDα and PSDß were significantly increased after tACS at T20, in which the effect sustained until T40. However, there was no differential effect by montages. There was no significant difference in the occurrence of sensations across the montages. The effectiveness of the blinding is supported by the participants' rate of guessing correctly. Conclusion: This study revealed an immediate inhibitory effect of tACS, regardless of the montages. This inhibitory effect sustained in the Oz-Cz montage but faded out in other montages after 20 min.

Experimentally induced myopia and myopic astigmatism alter retinal electrophysiology in chickens.

Myopia (or "short-sightedness") and astigmatism are major causes of visual impairment worldwide. Significant amounts of astigmatism are frequently observed in infants and have been associated with myopia development. Although it is well established that both myopia and astigmatism are associated with ocular structural changes from anterior to posterior segments, very little is known on how these refractive errors alter retinal functions. This study investigated the effects of experimentally induced myopia and myopic-astigmatism on retinal electrophysiology by using an image-guided, multifocal global flash stimulation in chickens, a widely used animal model for refractive error development. Myopia and myopic-astigmatism were experimentally induced, respectively, by wearing spherical (- 10 D, n = 12) and sphero-cylindrical lenses (- 6.00 DS/- 8.00 DCx90: Hyperopic With-The Rule, H-WTR, n = 15; - 6.00 DS/- 8.00 DCx180: Hyperopic Against-The-Rule, H-ATR, n = 11) monocularly for a week (post-hatching day 5 to 12). An aged-matched control group without any lens treatment provided normal data (n = 12). Multifocal electrophysiological results revealed significant regional variation in the amplitude of induced component (IC) (central greater than peripheral; both p < 0.05) in the normal and H-ATR groups, but not in the - 10 D and H-WTR groups. Most importantly, for the first time, our results showed that both H-WTR and H-ATR groups exhibited a significantly longer implicit time of the inner retinal response at the central region when compared to the normal and - 10 D groups, highlighting a significant role of astigmatism in retinal physiology.

Mechanistic Effects of Baicalein on Aqueous Humor Drainage and Intraocular Pressure.

Elevated intraocular pressure (IOP) is a major risk factor for glaucoma that results from impeded fluid drainage. The increase in outflow resistance is caused by trabecular meshwork (TM) cell dysfunction and excessive extracellular matrix (ECM) deposition. Baicalein (Ba) is a natural flavonoid and has been shown to regulate cell contraction, fluid secretion, and ECM remodeling in various cell types, suggesting the potential significance of regulating outflow resistance and IOP. We demonstrated that Ba significantly lowered the IOP by about 5 mmHg in living mice. Consistent with that, Ba increased the outflow facility by up to 90% in enucleated mouse eyes. The effects of Ba on cell volume regulation and contractility were examined in primary human TM (hTM) cells. We found that Ba (1-100 µM) had no effect on cell volume under iso-osmotic conditions but inhibited the regulatory volume decrease (RVD) by up to 70% under hypotonic challenge. In addition, Ba relaxed hTM cells via reduced myosin light chain (MLC) phosphorylation. Using iTRAQ-based quantitative proteomics, 47 proteins were significantly regulated in hTM cells after a 3-h Ba treatment. Ba significantly increased the expression of cathepsin B by 1.51-fold and downregulated the expression of D-dopachrome decarboxylase and pre-B-cell leukemia transcription factor-interacting protein 1 with a fold-change of 0.58 and 0.40, respectively. We suggest that a Ba-mediated increase in outflow facility is triggered by cell relaxation via MLC phosphorylation along with inhibiting RVD in hTM cells. The Ba-mediated changes in protein expression support the notion of altered ECM homeostasis, potentially contributing to a reduction of outflow resistance and thereby IOP.

Pain Symptoms in Optic Neuritis.

Signs and symptoms of optic neuritis (ON), an autoimmune disorder of the central nervous system (CNS), differ between patients. Pain, which is commonly reported by ON patients, may be the major reason for some patients to visit the clinic. This article reviews the presence of pain related to ON with respect to underlying disorders, including multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein associated disease (MOGAD). The aim of this review is to provide an overview of pain symptoms in accordance with the context of various pathophysiological explanations, assist in differential diagnosis of ON patients, especially at the onset of disease, and make recommendations to aid physicians make decisions for follow up diagnostic examinations.

Selective blue-filtering spectacle lens protected primary porcine RPE cells against light emitting diode-induced cell damage.

This study aimed to investigate whether use of a selective-blue-filtering (S-BF) lens can protect cultured primary porcine RPE cells against photo-irradiation. Transmittance of S-BF and UV-filtering (UVF) lenses was characterised spectrophotometrically. RPE cells were exposed to 1700 lux of white (peak λ at 443 and 533 nm; 0.44 mW/cm2) or blue (peak λ at 448 and 523 nm; 0.85 mW/cm2) LED light for 16 h to evaluate the influence of light source on the culture. The effect of the S-BF and UVF ophthalmic lenses on RPE cell cultures under blue light irradiation was then investigated. Cell viability was compared using trypan blue and MTT assays. Intracellular ROS production was detected by a fluorescein probe CM-H2DCFDA. Expression levels of catalase and Prdx3 were analysed by western blot. Trypan blue staining showed blue light caused more cell death than no light (p = 0.001) or white light (p = 0.005). MTT assay supported the hypothesis that exposure to blue light damaged RPE cells more severely than no light (p = 0.002) or white light (p = 0.014). Under blue light, use of the S-BF lens, which blocked 17% more blue light than the UVF lens, resulted in higher cellular viability (S-BF: 93.4±1.4% vs UVF: 90.6±1.4%; p = 0.022; MTT: 1.2-fold; p = 0.029). Blue and white light both significantly increased ROS production. The S-BF lens protected cells, resulting in lower levels of ROS and higher expression of catalase and Prdx3. To conclude, blue LED light exposure resulted in significant cytotoxicity to RPE cells. Partial blockage of blue light by an S-BF lens led to protective effects against retinal phototoxicity, which were mediated by reduction of ROS and increased levels of antioxidant enzymes.

Evaluation of an Optical Defocus Treatment for Myopia Progression Among Schoolchildren During the COVID-19 Pandemic.

Importance: Myopia progression has been found to be worsening during the COVID-19 pandemic. It is important to control the rapid myopia progression in this period. Objective: To analyze the association of COVID-19-related lockdown measures with myopia progression in schoolchildren and to compare the performance of defocus incorporated multiple segments (DIMS) lens with that of single vision lens (SVL) treatment in reducing myopia progression. Design, Setting, and Participants: This cohort study involved an exploratory, prespecified, comparison of 2 independent longitudinal studies performed at the same institute beginning in 2019. Data from Hong Kong schoolchildren (aged 7-13 years) were gathered and analyzed. Data analysis was performed from June to July 2021. Exposure: Schoolchildren in study 1 wore a DIMS lens for 18 months, and those in study 2 wore a SVL for 24 months. Main Outcomes and Measures: Cycloplegic spherical equivalent refraction and axial length were measured. Studies 1 and 2 started before the start of lockdown measures and continued throughout the lockdown. In both studies, periods of fewer and more COVID-19-related lockdown measures were identified. Because COVID-19 lockdown caused deviations from the visit schedule, myopia progression was normalized to 12-month change, which were compared between DIMS and SVL groups, also during the periods with less and more lockdown time. Results: There were 115 participants (58 girls [50.4%]; mean [SD] age, 10.3 [1.5] years) in the DIMS group; their mean (SD) baseline refraction was -4.02 (1.46) D. There were 56 participants (29 girls [51.8%]; mean [SD] age, 10.8 [1.5] years) in the SVL group; their mean (SD) baseline refraction was -2.99 (1.06) D. After controlling for the covariates, DIMS treatment was significantly associated with 34% less axial elongation (0.19 mm [95% CI, 0.16 to 0.22 mm] vs 0.30 mm [95% CI, 0.25 to 0.35 mm]; P < .001) and 46% less myopic progression after 12 months (-0.31 D [95% CI, -0.39 to -0.23 D] vs -0.57 D [95% CI, -0.69 to -0.45 D]; P = .001) compared with SVL treatment. In both the DIMS and SVL groups, more lockdown time was associated with significantly more spherical equivalent refraction (-0.54 D [95% CI, -0.64 to 0.44 D] vs -0.34 D [95% CI, -0.44 to -0.25 D]; P = .01) and axial length (0.29 mm [95% CI, 0.25 to 0.32 mm] vs 0.20 mm [95% CI, 0.16 to 0.24 mm]; P = .001) compared with less lockdown time. No significant interaction between treatment type and lockdown time was observed. Conclusions and Relevance: In this exploratory analysis, myopia progressed more rapidly in schoolchildren during the period when there were more COVID-19-related lockdown measures. However, optical treatment with DIMS was significantly associated with slower myopia progression compared with SVL treatment during the lockdown period.

The effect of spatially-related environmental risk factors in visual scenes on myopia.

Myopia, the most common refractive error, is estimated to affect over two billion people worldwide, especially children from East Asian regions. Children with early onset myopia have an increased risk of developing sight threatening complications in later life. In addition to the contribution of genetic factors, of which expression is controversially suggested to be subject to environmental regulation, various environmental factors, such as near-work, outdoor, and living environment, have also been determined to play significant roles in the development of refractive error, especially juvenile myopia. Cues from daily visual scenes, including lighting, spatial frequency, and optical defocus over the field of visual stimuli, are suggested to influence emmetropisation, thereby affecting myopia development and progression. These risk factors in visual scenes of the everyday life may explain the relationship between urbanicity and myopia prevalence. This review first summarises the previously reported associations between myopia development and everyday-life environments, including schooling, urban settings, and outdoors. Then, there is a discussion of the mechanisms hypothesised in the literature about the cues from different visual scenes of urbanicity in relation to myopia development.

Extrinsic and Intrinsic Factors Regulating Juvenile Refractive Development and Eye Growth.

Purpose: Peripheral refraction and accommodation are intrinsic factors that were once hypothesized to trigger myopia but are now controversial. Previously, home nearwork environment (i.e., extrinsic factor) was reported to be associated with myopia progression. In this study, we aimed to evaluate the potential interaction between extrinsic and intrinsic factors with juvenile refractive development. Methods: Nearwork environmental parameters were measured for 50 children (aged 9.3 ± 1.2 years), including net amount and dispersion of defocus. Refraction was measured at near distances and in central field (±30° horizontal) at 3m. The relative peripheral refraction (RPRE) was obtained and presented in a vectoral approach. The linear regression coefficient was extracted (mAcc) from the accommodative stimulus-response curve. RPRE was quadratically regressed against field eccentricity, and the first coefficients (aM, aJ0, aP90, and aP180) were extracted. Relationships between RPRE, baseline accommodation, and 1-year myopia progression (∆M), controlled for the nearwork environment, were evaluated. Results: Coefficients of RPRE were independent of ∆M. However, additional nearwork environmental parameters significantly improved the variance in ∆M explained by aM and aP180 (P < 0.03). The relationship between intrinsic factor and ∆M was stronger when the extrinsic risk was low (P ≤ 0.01), whereas the relationship was abolished when extrinsic risk was high. For mAcc, it also significantly improved the variance in ∆M explained by nearwork environmental parameters. Conclusions: The interaction between extrinsic (environment) and intrinsic (RPRE and accommodation) factors is speculated to contribute to juvenile myopia progression. Our findings may also explain the inconsistencies of such intrinsic factors in the literature.

Targeting Lysosomes to Reverse Hydroquinone-Induced Autophagy Defects and Oxidative Damage in Human Retinal Pigment Epithelial Cells.

In age-related macular degeneration (AMD), hydroquinone (HQ)-induced oxidative damage in retinal pigment epithelium (RPE) is believed to be an early event contributing to dysregulation of inflammatory cytokines and vascular endothelial growth factor (VEGF) homeostasis. However, the roles of antioxidant mechanisms, such as autophagy and the ubiquitin-proteasome system, in modulating HQ-induced oxidative damage in RPE is not well-understood. This study utilized an in-vitro AMD model involving the incubation of human RPE cells (ARPE-19) with HQ. In comparison to hydrogen peroxide (H2O2), HQ induced fewer reactive oxygen species (ROS) but more oxidative damage as characterized by protein carbonyl levels, mitochondrial dysfunction, and the loss of cell viability. HQ blocked the autophagy flux and increased proteasome activity, whereas H2O2 did the opposite. Moreover, the lysosomal membrane-stabilizing protein LAMP2 and cathepsin D levels declined with HQ exposure, suggesting loss of lysosomal membrane integrity and function. Accordingly, HQ induced lysosomal alkalization, thereby compromising the acidic pH needed for optimal lysosomal degradation. Pretreatment with MG132, a proteasome inhibitor and lysosomal stabilizer, upregulated LAMP2 and autophagy and prevented HQ-induced oxidative damage in wildtype RPE cells but not cells transfected with shRNA against ATG5. This study demonstrated that lysosomal dysfunction underlies autophagy defects and oxidative damage induced by HQ in human RPE cells and supports lysosomal stabilization with the proteasome inhibitor MG132 as a potential remedy for oxidative damage in RPE and AMD.

Utilizing Advanced Technology to Facilitate Diagnosis of Rare Retinal Disorders: A Case of Bietti Crystalline Dystrophy.

SIGNIFICANCE: Optometrists, as primary eye care providers, encounter patients with rare ocular disease such as Bietti crystalline dystrophy from time to time. Using advanced technologies, which are also useful in managing common ocular conditions, to facilitate a prompt diagnosis is highly recommended. PURPOSE: This report describes a patient with clinically diagnosed Bietti crystalline dystrophy with findings on funduscopy, multimodal imaging, and visual electrophysiology. CASE REPORT: A 41-year-old Chinese woman who had subjectively progressing dimmed vision (especially in the left eye) for 9 months was referred to our clinic to test for retinitis pigmentosa. Best-corrected visual acuities were 6/6 and 6/7.6 in the right and left eyes, respectively. Funduscopy revealed multiple crystalline deposits on the posterior pole in both eyes. The 30-2 perimetry displayed bi-inferotemporal scotoma (left > right eye). Scotopic flash electroretinogram (ERG) yielded a normal result, whereas photopic ERG was slightly attenuated. Electro-oculogram showed an abnormal adaptation time course of the retinal pigmented epithelium (RPE). Multifocal ERG revealed a decreased central retinal response, but paracentral responses were relatively better preserved. Optical coherence tomography showed multiple patches of RPE atrophy, with disruption of the left ellipsoid zone. Outer retinal tubulations, hyperreflective dots on RPE-Bruch's membrane interface, and intraretinal bright spots were also identified. CONCLUSIONS: Rare ocular diseases like Bietti crystalline dystrophy can be encountered by optometrists. This case report shows the ophthalmic findings of a rare chorioretinal dystrophy and provides insight on how to better use advanced equipment in an optometric practice to facilitate prompt diagnoses.

Autophagy Upregulation by the TFEB Inducer Trehalose Protects against Oxidative Damage and Cell Death Associated with NRF2 Inhibition in Human RPE Cells.

Trehalose is a natural dietary molecule that has shown antiaging and neuroprotective effects in several animal models of neurodegenerative diseases. The role of trehalose in the management of age-related macular degeneration (AMD) is yet to be investigated and whether trehalose could be a remedy for the treatment of diseases linked to oxidative stress and NRF2 dysregulation. Here, we showed that incubation of human retinal pigment epithelial (RPE) cells with trehalose enhanced the mRNA and protein expressions of TFEB, autophagy genes ATG5 and ATG7, as well as protein expressions of macroautophagy markers, LC3B and p62/SQTM1, and the chaperone-mediated autophagy (CMA) receptor LAMP2. Cathepsin D, a hydrolytic lysosomal enzyme, was also increased by trehalose, indicating higher proteolytic activity. Moreover, trehalose upregulated autophagy flux evident by an increase in the endogenous LC3B level, and accumulation of GFP-LC3B puncta and free GFP fragments in GFP-LC3 - expressing cells in the presence of chloroquine. In addition, the mRNA levels of key molecular targets implicated in RPE damage and AMD, such as vascular endothelial growth factor- (VEGF-) A and heat shock protein 27 (HSP27), were downregulated, whereas NRF2 was upregulated by trehalose. Subsequently, we mimicked in vitro AMD conditions using hydroquinone (HQ) as the oxidative insult on RPE cells and evaluated the cytoprotective effect of trehalose compared to vehicle treatment. HQ depleted NRF2, increased oxidative stress, and reduced the viability of cells, while trehalose pretreatment protected against HQ-induced toxicity. The cytoprotection by trehalose was dependent on autophagy but not NRF2 activation, since autophagy inhibition by shRNA knockdown of ATG5 led to a loss of the protective effect. The results support the transcriptional upregulation of TFEB and autophagy by trehalose and its protection against HQ-induced oxidative damage in RPE cells. Further investigation is, therefore, warranted into the therapeutic value of trehalose in alleviating AMD and retinal diseases associated with impaired NRF2 antioxidant defense.

Longitudinal outcomes of circumlimbal suture model-induced chronic ocular hypertension in Sprague-Dawley albino rats.

PURPOSE: To characterise longitudinal structural and functional changes in albino Sprague-Dawley rats following circumlimbal suture ocular hypertension (OHT) induction. METHODS: Ten-week-old rats (n = 24) underwent suture implantation around the limbal region in both eyes. On the next day, the suture was removed from one eye (control eyes) and left intact in the other eye (OHT eyes) of each animal. Intraocular pressure (IOP) was monitored weekly twice for the next 15 weeks. Optical coherence tomography (OCT) and electroretinogram (ERG) were measured at baseline and weeks 4, 8, 12, and 15, and eyes were then collected for histological assessment. RESULTS: Sutured eyes (n = 12) developed IOP elevation of ~ 50% in the first 2 weeks that was sustained at ~ 25% above the control eye up to week 15 (p = 0.001). Animals with insufficient IOP elevation (n = 6), corneal changes (n = 3), and attrition (n = 3) were excluded from the analysis. OHT eyes developed significant retinal nerve fibre layer (RNFL) thinning (week 4: - 19 ± 14%, p = 0.10; week 8: - 17 ± 12%, p = 0.04; week 12: - 16 ± 10%, p = 0.04, relative to baseline) and reduction in retinal ganglion cell (RGC) density (- 32 ± 26%, p = 0.02). At week 15, both inner (9 ± 7%, p = 0.01) and outer retinal layer thicknesses (6.0 ± 5%, p = 0.001) showed a mild increase in thicknesses. The positive scotopic threshold response (- 28 ± 25%, p = 0.04) and a-wave were significantly reduced at week 12 (- 35 ± 21%; p = 0.04), whereas b-wave was not significantly affected (week 12: - 18 ± 27%, p = 0.24). CONCLUSION: The circumlimbal suture model produced a chronic, moderate IOP elevation in an albino strain that led to RNFL thinning and reduced RGC density along with the reductions in ganglion and photoreceptoral cell functions. There was a small thickening in both outer and inner retinal layers.

The diversified defocus profile of the near-work environment and myopia development.

PURPOSE: To quantify the defocus characteristics in the near-work environment at home and investigate the relationship with subsequent myopia progression. METHODS: Fifty subjects (aged 7-12 years) were recruited and followed for 1 year. The home near-work environment (writing desk) was measured at a baseline home-visit using the Kinect-for-Windows to capture a 3-dimensional image. The depth values of the image were then converted into scene defocus with respect to the subject's viewpoint. The defocus characteristics were quantified as the dioptric volume (the total amount of net defocus, or DV) and standard deviation of the defocus values (SDD ). Information on home size, time spent outdoors, and in front of a desk were also obtained. Univariate correlation, and multivariate regression were used to assess the association between myopia progression, defocus characteristics, and other co-variates. RESULTS: The baseline spherical equivalent refraction (M) and refraction change over 1 year (∆M) were - 1.51 ± 2.02 D and - 0.56 ± 0.45 D respectively. DV was not significantly correlated with ∆M (Spearman's ρ = -0.25, p = 0.08), while SDD was negatively correlated to ∆M (Spearman's ρ = -0.42, p = 0.003). Although SDD was not a significant predictor in multivariate analysis, the regional DV at 15°-20° eccentricity was significant (p = 0.001). Home size (F2,50  = 7.01, p = 0.002) and time spent outdoors (Independent t = -2.13, p = 0.04) were also associated with ∆M, but not time spent in front of desk (Independent t = 0.78, p = 0.44). CONCLUSION: The defocus profile in the home environment within the para-central field of view is associated with childhood refractive error development.